As compared to healthy elderly, frail elderly were found to have a lower percentage of pDCs that produce interferon-alpha (IFN-α) — a protein that regulates the immune response to viral infections.
The finding holds significance as it shows the need to support pDC activity in elderly at risk of frailty.
Frailty is a state between a normal healthy condition and the need for nursing care, Kirin said, citing a definition proposed by the Japanese Society of Geriatrics and Gerontology in 2014.
It can also be referred as a common clinical syndrome in older adults that carries an increased risk for poor health outcomes, including falls, incident disability, hospitalization, and mortality.
Study method
The study was jointly conducted by Kirin and the National Center for Geriatrics and Gerontology in 2023.
During the study, Kirin measured the pDC activities in the blood samples from 141 elderly aged 65 and above.
These 141 elderly were participating in a large-scale cohort study known as the National Center for Geriatrics and Gerontology - Study of Geriatric Syndromes (NCGG - SGS).
The NCGG-SGS is a longitudinal study of aging conducted by the National Institute on Longevity since 2011. It analyzes data to understand the risk of geriatric syndromes that occur with aging and aims to identify effective ways to treat them.
These 141 elderly were selected as they met both the inclusion and exclusion criteria, including not having a history of diabetes, chronic inflammatory diseases, gastrointestinal or other immune-related diseases to ensure accurate evaluation of their immune function.
Among these 141 elderly, 76 were in a healthy or robust condition, 52 were at the pre-frail and 13 in the frail condition.
Their blood samples were drawn and their pDC activities were assessed by measuring their blood cells’ responsiveness to influenza virus stimulation.
pDC activity was evaluated by measuring the amount of pDCs producing IFN-α — a protein that regulates the immune response to viral infections.
During the assessment, peripheral blood mononuclear cells (PBMCs) were isolated from the participants’ blood samples.
These PBMCs were then exposed to the H1N1 influenza virus, and the proportion of pDCs producing IFN-α was evaluated using flow cytometry.
Findings
Results showed that the median value of pDC activity across all participants was 2.78% — and this value was used as a benchmark to determine low and high pDC activities.
In this case, anything below 2.78% were referred to as having low pDC activity, while anything above 2.78% were defined as having high pDC activity.
Having a low pDC activity is not desirable as it means a weakened capability to fight off the influenza virus.
As compared to healthy participants, it was found that the odds ratio of having high pDC activity was only about one-fifth or 0.21 in frail participants, which was a statistically significant finding.
“There was a significantly higher population of frail individuals with severely reduced responsiveness, suggesting diminished capability of pDCs in mounting an anti-virus immune reaction,” Sugihara Yoshiko, researcher at Kirin Holdings Health Science Research Institute, told NutraIngredients.
The finding aligns with the researchers’ initial hypothesis that pDC activity is lower in frail elderly.
“The finding aligns with our initial hypothesis as individuals with frailty are known to be more susceptible to infections such as influenza pneumonia, and they tend to experience more severe outcomes.”
Causal relationship to be determined
However, it remains unclear if there is a direct causal relationship between pDC activity and frailty.
“It remains unclear whether reduced pDC activity leads to frailty or frailty causes a decrease in pDC action.
“We believe that the mechanism could be that a decreased pDC activity increases the susceptibility to infections, which may contribute to the onset or worsening of frailty.
“It is also possible that both factors influence each other bidirectionally and the progression of frailty will reduce immune competence...That said, this study did not clarify the underlying mechanisms,” said Sugihara.
As such, there are plans to find out if there is a causal relationship between pDC activity and frailty in the future.
This could be done via prospective cohort studies or interventional trials.
Prior to this finding, pDC activity is already established as an indicator of immune function.
In recent years, Kirin has developed a series of health supplements and functional food and beverages that support pDC activities using the postbiotic Lactococcus lactis strain Plasma.
The postbiotic is also commercially available as LC-plasma or IMMUSE.
The need to maintain pDC activity
Kirin believes that the finding showed the need to support pDC activity — especially among elderly who are at risk of frailty.
“If our results encourage such populations to adopt immune-supportive habits, like consuming Lactococcus lactis strains plasma, we see that as a meaningful application and we hope to continue promoting this message to older adults,” said Sugihara.
Inspiration behind research
Taking into account the backdrop of a super-aging society, the research aimed to find out if there is a relationship between aging and immune function.
“At Kirin Holdings, we have been studying pDC activities in healthy adults for many years. However, we want to expand our focus to all the adults who are often described as immuno-compromised and who are just more vulnerable to infections.
“While we already know that pDC activities degrades with age, no research has clearly compared pDC activity loss and frailty.
“Additionally, frailty is an important concept in aging populations, and we want to explore how pDC function is involved in this,” said Sugihara.
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